The purpose of this project is to increase our understanding of the interactions between the endocrine and immune systems in both experimental animals and humans. Several immune system products, such as the cytokines Tumor Necrosis Factor- alpha (TNF-a), Interleukin-1, and Interleukin-6 (IL-6) activate the hypothalamic-pituitary-adrenal axis and through it suppress and restrain the inflammatory/immune response. Human fat examined in situ by microperfusion produces not only leptin, but also TNF- alpha and IL-6. We recently demonstrated that corticotropin-releasing hormone (CRH) is produced locally at sites of inflammation and has profound pro-inflammatory effects at an autocrine/paracrine level. CRH is a potent degranulator of mast cells, a phenomenon that can be inhibited by a nonpeptide CRH antagonist, specific for type 1 receptors called antalarmin. CRH was found in the ovary and endometrium where it may participate in the inflammatory phenomena of ovulation, luteolysis, blastocyst implantation, and menstruation. - Human Subjects